Acadia Pharmaceuticals reports that pimavanserin was particularly effective in treating psychosis in Alzheimer’s disease patients who had severe psychotic symptoms, without triggering a deterioration in their cognition.
The information, which stems from additional analyses of data gathered in a Phase 2 trial of pimavanserin in Alzheimer’s patients, was presented at the recent 10th Clinical Trials on Alzheimer’s Disease (CTAD) meeting in Boston.
While the company announced in December 2016 that the study met its primary goal of reducing psychotic symptoms in Alzheimer’s patients, the presentation covered a subgroup analysis and additional assessments of exploratory outcome measures.
Pimavanserin is approved to treat psychosis in Parkinson’s disease patients under the brand name Nuplazid.
“In the Phase II -019 Study, pimavanserin significantly reduced psychosis in patients with Alzheimer’s disease without negatively impacting cognition,” Clive Ballard, executive dean of the University of Exeter Medical School, who presented the data at the meeting, said in a press release.
The study, which the company refers to as -019, showed that the therapy reduced psychosis compared to placebo after six weeks of treatment. At six weeks, 55.2 percent of pimavanserin-treated patients had improved by at least 30 percent, compared to only 37.4 percent of those in the placebo group.
But an analysis of those patients who entered the study with more severe psychosis (about one-third of total group) revealed even better results — a significant reduction in psychotic symptoms. The number of patients who improved by at least 30 percent was also greater than in the entire study group — 88.9 percent of pimavanserin-treated patients improved, compared to 43.3 of those receiving placebo.
Acadia again underscored that the treatment was effective without causing patients’ cognition to worsen. Current antipsychotics have been linked to increased mortality and morbidity when used in patients with dementia, and are not approved for use in those with Alzheimer’s disease.
Another presentation at the same session underscored that off-label use of antipsychotics in Alzheimer’s patients has little evidence of efficacy and is linked to a significant acceleration of cognitive decline.
That leaves the nearly one-third of Alzheimer’s patients who develop psychosis without approved treatment options.
“Pimavanserin also had a favorable tolerability profile compared to known adverse effects of current antipsychotics,” Ballard said. “With no approved treatment for dementia-related psychosis, there is a significant unmet need. The results of the study indicate that pimavanserin could be an important new treatment option for this elderly and underserved patient population.”
Nevertheless, the presentation also showed that the study failed to meet its secondary goals, a reduction in agitation and changes on a global impression of change test. The lack of changes on the global impression of change scale, however, supports the claim that pimavanserin does not cause a deterioration in cognition.
The treatment also did not appear to impact exploratory measure of daily living activities.
Possibly a more worrisome finding is that researchers found no significant difference between the pimavanserin and placebo groups when measuring the severity of psychosis at week 12. Rather, researchers said that the changes seen at six weeks were maintained in the pimavanserin group, suggesting that placebo-treated patients may have improved during the time between six and 12 weeks.
The treatment is now being explored in a Phase 3 trial, called HARMONY (NCT03325556), in patients with dementia-related psychosis. In addition to Alzheimer’s disease, the study includes people with dementia with Lewy bodies, Parkinson’s disease dementia, vascular dementia, and frontotemporal dementia.
All patients will first be treated with pimavanserin for 8 to 12 weeks to resolve psychosis. After that, patients will be randomized to either pimavanserin or a placebo. Rather than measuring the severity of psychotic symptoms, the new study will explore if pimavanserin can prevent relapses of psychotic symptoms in these patients over 26 weeks.
The trial, which is currently recruiting participants, will run until 2020. More information, including contact details, is available on the study’s registration page.